Manfred was the last King of Sicily from the Hohenstaufen dynasty, reigning from 1258 until his death. The natural son of the Holy Roman Emperor Frederick II, Manfred became regent over the kingdom of Sicily on behalf of his nephew Conradin in 1254. As regent he subdued rebellions in the kingdom, until in 1258 he usurped Conradin's rule. After an initial attempt to appease Pope Innocent IV he took up the ongoing conflict between the Hohenstaufens and the papacy through combat and political alliances. He defeated the papal army at Foggia on 2 December 1254. Excommunicated by three successive popes, Manfred was the target of a Crusade (1255–66) called first by Pope Alexander IV and then by Urban IV. Nothing came of Alexander's call, but Urban enlisted the aid of Charles of Anjou in overthrowing Manfred. Manfred was killed during his defeat by Charles at the Battle of Benevento, and Charles assumed kingship of Sicily.

The Hohenstaufen dynasty, also known as the Staufer, was a noble family of unclear origin that rose to rule the Duchy of Swabia from 1079, and to royal rule in the Holy Roman Empire during the Middle Ages from 1138 until 1254. The dynasty's most prominent rulers – Frederick I (1155), Henry VI (1191) and Frederick II (1220) – ascended the imperial throne and also reigned over Italy and Burgundy. The non-contemporary name of 'Hohenstaufen' is derived from the family's Hohenstaufen Castle on Hohenstaufen mountain at the northern fringes of the Swabian Jura, near the town of Göppingen. Under Hohenstaufen rule, the Holy Roman Empire reached its greatest territorial extent from 1155 to 1268.